Genetic conservation of Cytauxzoon felis antigens and mRNA expression in the schizont life-stage

Khana, Daven B.; Peterson, David S.; Stanton, James B.; Schreeg, Megan E.; Birkenheuer, Adam J.; Tarigo, Jaime L.

doi:10.1016/j.vetpar.2018.10.007

Cited by 5 publications

(3 citation statements)

References 21 publications

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“…The C. felis gene is in a syntenic genomic location as its ortholog in T. parva . The cf63 antigen has previously been identified as a potential vaccine candidate against cytauxzoonosis in domestic cats, based on a high level of conservation and expression in the schizont stage of the life cycle; however, the function of this gene is unknown (Khana et al 2018 ). Another interesting result of this BLAST search was that while the conserved region was found in 5–12 genes in T. parva , T. annulata , and T. orientalis (the cattle-infecting Theileria species), it matched to 63 genes in T. equi , suggesting a more substantive role in that species.…”

Section: Resultsmentioning

confidence: 99%

“…4). The suggestion by Khana et al ( 2018 ) that the cf63 antigen in C. felis , which contains a segment with significant sequence similarity to this conserved 5′ domain, be considered as a vaccine candidate against disease caused by C. felis infection in cats, brings up the interesting possibility that these two genes in T. parva may be worthy of further study as vaccine candidates.…”

Section: Discussionmentioning

confidence: 99%

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The Hypervariable Tpr Multigene Family of Theileria Parasites, Defined by a Conserved, Membrane-Associated, C-Terminal Domain, Includes Several Copies with Defined Orthology Between Species

Palmateer,

Munro,

Nagaraj

et al. 2023

J Mol Evol

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Multigene families often play an important role in host-parasite interactions. One of the largest multigene families in Theileria parva, the causative agent of East Coast fever, is the T. parva repeat (Tpr) gene family. The function of the putative Tpr proteins remains unknown. The initial publication of the T. parva reference genome identified 39 Tpr family open reading frames (ORFs) sharing a conserved C-terminal domain. Twenty-eight of these are clustered in a central region of chromosome 3, termed the “Tpr locus”, while others are dispersed throughout all four nuclear chromosomes. The Tpr locus contains three of the four assembly gaps remaining in the genome, suggesting the presence of additional, as yet uncharacterized, Tpr gene copies. Here, we describe the use of long-read sequencing to attempt to close the gaps in the reference assembly of T. parva (located among multigene families clusters), characterize the full complement of Tpr family ORFs in the T. parva reference genome, and evaluate their evolutionary relationship with Tpr homologs in other Theileria species. We identify three new Tpr family genes in the T. parva reference genome and show that sequence similarity among paralogs in the Tpr locus is significantly higher than between genes outside the Tpr locus. We also identify sequences homologous to the conserved C-terminal domain in five additional Theileria species. Using these sequences, we show that the evolution of this gene family involves conservation of a few orthologs across species, combined with gene gains/losses, and species-specific expansions.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Hypervariable Tpr Multigene Family of Theileria Parasites, Defined by a Conserved, Membrane-Associated, C-Terminal Domain, Includes Several Copies with Defined Orthology Between Species

Palmateer,

Munro,

Nagaraj

et al. 2023

J Mol Evol

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“…The ultimate goal of employing a replication-defective AdHu5 vector vaccine in this study was to effectively deliver antigen-coding genes inside host immune cells that could then express the antigens and initiate a sufficient humoral and cellular immune response to C. felis -specific proteins, c88 and cf76. These two antigens were selected based on previous studies that showed that these proteins were expressed during the schizogenous phase of C. felis (the most crucial stage for parasite replication and clinical disease) and are known to be highly immunogenic, making them promising vaccine candidates [ 14 , 20 , 49 , 50 ]. We then demonstrated a significant cell-mediated (c88 and cf76) and humoral immune response (c88 only) to vaccine epitopes in vaccinated cats.…”

Section: Discussionmentioning

confidence: 99%

A Novel Vaccine Strategy to Prevent Cytauxzoonosis in Domestic Cats

et al. 2023

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Cytauxzoonosis is caused by Cytauxzoon felis (C. felis), a tick-borne parasite that causes severe disease in domestic cats in the United States. Currently, there is no vaccine to prevent this fatal disease, as traditional vaccine development strategies have been limited by the inability to culture this parasite in vitro. Here, we used a replication-defective human adenoviral vector (AdHu5) to deliver C. felis-specific immunogenic antigens and induce a cell-mediated and humoral immune response in cats. Cats (n = 6 per group) received either the vaccine or placebo in two doses, 4 weeks apart, followed by experimental challenge with C. felis at 5 weeks post-second dose. While the vaccine induced significant cell-mediated and humoral immune responses in immunized cats, it did not ultimately prevent infection with C. felis. However, immunization significantly delayed the onset of clinical signs and reduced febrility during C. felis infection. This AdHu5 vaccine platform shows promising results as a vaccination strategy against cytauxzoonosis.

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